Tauroursodeoxycholic acid (TUDCA) is neuroprotective in a chronic mouse model of Parkinson’s disease
Por:
Cuevas E., Burks S., Raymick J., Robinson B., Gómez-Crisóstomo N.P., Escudero-Lourdes C., Lopez A.G.G., Chigurupati S., Hanig J., Ferguson S.A., Sarkar S.
Publicada:
3 jul 2022
Ahead of Print:
1 ene 2020
Resumen:
Objective: Parkinson’s disease (PD) is a progressive motor disease of unknown etiology. Although neuroprotective ability of endogenous bile acid, tauroursodeoxycholic acid (TUDCA), shown in various diseases, including an acute model of PD,the potential therapeutic role of TUDCA in progressive models of PD that exhibit all aspects of PD has not been elucidated. In the present study, mice were assigned to one of four treatment groups: (1) Probenecid (PROB); (2) TUDCA, (3) MPTP + PROB (MPTPp); and (3) TUDCA + MPTPp. Methods: Markers for dopaminergic function, neuroinflammation, oxidative stress and autophagy were assessed using high performance liquid chromatography (HPLC), immunohistochemistry (IHC) and western blot (WB) methods. Locomotion was measured before and after treatments. Results: MPTPp decreased the expression of dopamine transporters (DAT) and tyrosine hydroxylase (TH), indicating dopaminergic damage, and induced microglial and astroglial activation as demonstrated by IHC analysis. MPTPp also decreased DA and its metabolites as demonstrated by HPLC analysis. Further, MPTPp-induced protein oxidation; increased LAMP-1 expression indicated autophagy and the promotion of alpha-synuclein (a-SYN) aggregation. Discussion: Pretreatment with TUDCA protected against dopaminergic neuronal damage, prevented the microglial and astroglial activation, as well as the DA and DOPAC reductions caused by MPTPp. TUDCA by itself did not produce any significant change, with data similar to the negative control group. Pretreatment with TUDCA prevented protein oxidation and autophagy, in addition to inhibiting a-SYN aggregation. Although TUDCA pretreatment did not significantly affect locomotion, only acute treatment effects were measured, indicating more extensive assessments may be necessary to reveal potential therapeutic effects on behavior. Together, these results suggest that autophagy may be involved in the progression of PD and that TUDCA may attenuate these effects. The efficacy of TUDCA as a novel therapy in patients with PD clearly warrants further study. © 2020 Informa UK Limited, trading as Taylor & Francis Group.
Filiaciones:
Cuevas E.:
Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, United States
Burks S.:
Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, United States
Raymick J.:
Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, United States
Robinson B.:
Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, United States
Gómez-Crisóstomo N.P.:
Universidad Autonoma Juarez de Tabasco, Tabasco, Mexico
Escudero-Lourdes C.:
National Center for Toxicological ResearchFDA, United States
Lopez A.G.G.:
Escuela Nacional Preparatoria-UNAM, Mexico
Chigurupati S.:
Office of Regulatory Affairs, Office of Regulatory Science, Food and Drug Administration, Rockville, MD, United States
Hanig J.:
Office of Testing & Research, CDER/FDA, White Oak, MD, United States
Ferguson S.A.:
Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, United States
Sarkar S.:
Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, United States
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